Evaluation of Effective Half-Life and Its Impact on Time to Steady State for Oral MeltDose Tacrolimus (LCPT) in De Novo Kidney Transplant Recipients.

Background: For extended-release drug formulations, effective half-life (t1/2eff) is a relevant pharmacokinetic parameter to inform dosing strategies and time to reach steady state. Tacrolimus, an immunosuppressant commonly used for the prophylaxis of organ rejection in transplant patients, is available as both immediate- and extended-release formulations. To the best of our knowledge, the t1/2eff of tacrolimus from these different formulations has not yet been assessed.

Pretransplant Cognitive Function and Kidney Transplant Outcomes: A Prospective Cohort Study.

Background & Hypothesis: Cognitive impairment is common in patients being evaluated for a kidney transplant (KT). The association between pretransplant cognitive function and posttransplant outcomes is unclear.

Study Design: We performed a prospective cohort study to assess the association between pretransplant cognitive function and clinically relevant posttransplant outcomes.

Pre-transplant cognitive screening is a poor predictor of post-transplant cognitive status.

Introduction: Transplant centers hesitate to transplant patients with cognitive impairment. It is unclear if pre-kidney transplant (KT) cognitive screening can predict post-KT cognitive function.

Methods: We evaluated pre- to post-KT cognitive function with the Montreal Cognitive Assessment (MoCA) in a cohort of 108 patients.

Posttransplant proteinuria due to Apolipoprotein E2 deposition in a kidney allograft.

Lipoprotein deposition disorders limited to the kidney and causing proteinuria are rare. We present a case of nephrotic range proteinuria presenting within 4 months after deceased donor renal transplantation in a patient with end-stage kidney disease presumed secondary to hypertension. Two transplant kidney biopsies were performed sixteen weeks after transplantation, and one year after the first biopsy, both showing lipoprotein deposits in the glomeruli, progressive focal segmental glomerulosclerosis, and effacement of visceral foot processes.

Podocyte stress and detachment measured in urine are related to mean arterial pressure in healthy humans.

Hypertension-associated progressive glomerulosclerosis is a significant driver of both de novo and all-cause chronic kidney disease leading to end-stage kidney failure. The progression of glomerular disease proceeds via continuing depletion of podocytes from the glomeruli into the ultrafiltrate. To non-invasively assess injury patterns associated with mean arterial pressure (MAP), we conducted an observational study of 87 healthy normotensive individuals who were cleared for living kidney donation.

Subclinical Cognitive Impairment and Listing for Kidney Transplantation.

Background And Objectives: Cognitive impairment is common in patients with kidney disease and can affect physicians' perception and/or patients' ability to complete the pretransplant evaluation. We examined whether cognitive impairment influences the likelihood for transplant listing and whether patients with cognitive impairment take longer to be listed.

Design, Setting, Participants, & Measurements: We conducted a single-center longitudinal cohort study.

Accelerated podocyte detachment early after kidney transplantation is related to long-term allograft loss of function.

Background: Kidney allograft half-life has not improved despite excellent short-term survival. Recent long-term surveillance biopsy studies identify accumulating glomerulosclerosis (GS) to be associated with late allograft loss. While podocyte depletion is well known to drive proteinuria and GS in animal models and human glomerular diseases, its role in renal allograft loss of function is generally not recognized.

A LASSO Method to Identify Protein Signature Predicting Post-transplant Renal Graft Survival.

Identifying novel biomarkers to predict renal graft survival is important in post-transplant clinical practice. Serum creatinine, currently the most popular surrogate biomarker, offers limited information of the underlying allograft profiles. It is known to perform unsatisfactorily to predict renal function.

Temporal trends, center-level variation, and the impact of prevalent state obesity rates on acceptance of obese living kidney donors.

The impact of pre-donation obesity on long-term outcomes of living kidney donors remains controversial. Published guidelines offer varying recommendations regarding BMI (kg/m ) thresholds for donor acceptance. We examined temporal and center-level variation in BMI of accepted donors across US transplant centers.

The Impact of Obesity on Allograft Failure After Kidney Transplantation: A Competing Risks Analysis.

Background: The impact of pretransplant body mass index (BMI) on long-term allograft outcomes after kidney transplantation remains controversial. The conventional approach of using Kaplan-Meier method to calculate the cumulative risk of death-censored allograft failure may overestimate the risk of failure especially when competing failure risks are present.

Method: A retrospective cohort of adult first-time kidney transplant recipients was drawn from the Organ Procurement and Transplantation Network database (2001 to 2009).

Identification of a protein signature in renal allograft rejection.

Purpose: Serum creatinine functions as a poor surrogate marker of renal allograft dysfunction and long-term graft survival. By measuring multiple proteins simultaneously in the serum of transplant patients, we can identify unique protein signatures of graft dysfunction.

Experimental Design: We utilized training and validation cohorts composed of healthy and volunteer subjects, stable renal transplant patients, and renal transplant patients experiencing acute allograft rejection.

Mycophenolic acid pharmacokinetics in lung transplant recipients with cystic fibrosis.

Background: Lung transplantation is an established treatment for cystic fibrosis (CF) patients with end-stage lung disease. Current immunosuppression includes the prodrug mycophenolate mofetil (MMF), which has led to improved transplant outcomes. Given the pancreatic insufficiency and malabsorption in CF patients, some transplant centers give higher doses of MMF to these patients based on lower predose levels (C(0)), even though C(0) values correlate poorly with mycophenolic acid (MPA) exposure.

A history of chronic opioid usage prior to kidney transplantation may be associated with increased mortality risk.

Chronic opioid usage (COU) for analgesia is common among patients with end-stage renal disease. In order to test whether a prior history of COU negatively affects post-kidney transplant outcomes, we retrospectively examined clinical outcomes in adult kidney transplant patients. Among 1064 adult kidney transplant patients, 452 (42.

The time interval between kidney and pancreas transplantation and the clinical outcomes of pancreas after kidney transplantation.

Pancreas after kidney (PAK) transplantation is one of the accepted pancreas transplant modalities. We studied the impact of time interval between kidney and pancreas transplantation on the outcomes of PAK transplantation. Using OPTN/SRTR data, we included 1853 PAK transplants performed between 1996 and 2005 with follow-up until November 1, 2008.

Lymphoma after solid organ transplantation: risk, response to therapy, and survival at a transplantation center.

Purpose: We studied the incidence, risk factors, treatment, and outcomes of post-transplantation lymphoproliferative disorder (PTLD) that occurred at the University of Michigan since 1964.

Patients And Methods: We identified 7,040 patients who received solid organ transplantation (SOT) and post-transplantation immunosuppressive therapy. Seventy-eight patients developed PTLD.

Impact of changing from cyclosporine to tacrolimus on pharmacokinetics of mycophenolic acid in renal transplant recipients with diabetes.

The rate of mycophenolic acid (MPA) absorption after oral administration of mycophenolate mofetil (MMF) is delayed in patients with diabetes. Cyclosporine (CsA) decreases MPA exposure by inhibiting enterohepatic recirculation of MPA/MPA glucuronide, and tacrolimus (TRL) may alter the rate and extent of MPA absorption due to its prokinetic properties especially in patients with diabetic gastroparesis. This study evaluated the effect of changing from CsA to TRL on pharmacokinetics of MPA in stable renal transplant recipients with long-standing diabetes.

Impact of simultaneous pancreas and kidney transplantation on cardiovascular risk factors in patients with type 1 diabetes mellitus.

We retrospectively investigated the impact of pancreas transplantation on cardiovascular disease risk factors in patients with type 1 diabetic end-stage renal disease (ESRD). Two cohorts of patients, 44 simultaneous pancreas and kidney transplant patients (SPK) and 30 kidney transplant-alone patients (KTA), were included. Univariate and multivariate analyses were performed.

Therapeutic drug monitoring of mycophenolic acid in solid organ transplant patients treated with mycophenolate mofetil: review of the literature.

Mycophenolate mofetil (MMF) has conventionally been administered at a fixed dose without routinely monitoring blood levels of mycophenolic acid (MPA), the active metabolite. The contribution of therapeutic drug monitoring (TDM) during MMF therapy remains controversial. A literature review was performed to explore the usefulness of TDM for MPA in solid organ transplantation.

Renal allograft survival in transplant recipients with focal segmental glomerulosclerosis.

Previous literature suggests that the recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation is more common in recipients who have received an HLA-identical living-related (LRD) transplant. To address the question if FSGS patients can safely receive a 6-antigen match LRD kidney transplant, we analyzed death-censored renal allograft survival data of FSGS patients from the United States Renal Data System database (USRDS). Using the USRDS and the U.

Evaluation of pancreatic allograft dysfunction by laparoscopic biopsy.

Background: Histologic evaluation of a failing pancreatic allograft is necessary for accurate classification of graft dysfunction. Unlike percutaneous or transcystoscopic techniques, laparoscopic biopsy allows visualization of the allograft in addition to obtaining tissue for histologic examination.

Methods: We retrospectively reviewed all laparoscopic pancreas transplant biopsies performed over a 15-month period ending February 2002.

Renal allograft survival in patients with oxalosis.

Background: Primary hyperoxaluria is a rare autosomal recessive metabolic disease that often progresses to end-stage renal disease (ESRD). Liver transplantation is curative for patients with the alanine: glyoxylate aminotransferase deficiency. For oxalosis patients with minor enzyme deficiencies, renal transplantation may be the therapy of choice although concern exists about recurrence of oxalosis in the transplanted kidney.

Interaction between donor and recipient age in determining the risk of chronic renal allograft failure.

Objectives: Donor age is a known risk factor for chronic allograft failure (CAF) in renal transplant recipients. We have recently shown that advanced recipient age is also a risk factor for CAF. To investigate the interaction between donor and recipient age, we analyzed 40,289 primary solitary Caucasian adult renal transplants registered at the United States Renal Data System (USRDS) from 1988 to 1997.